质子感知受体与肿瘤发生和肿瘤转移之间的关系

Relationship between Proton-sensing G-protein Coupled Receptors and Tumorigenesis and Tumor Metastasis

G蛋白偶联受体家族卵巢癌G蛋白偶联受体1(ovarian cancer G protein-coupled receptor 1,OGR1)亚家族的OGR1、T细胞死亡偶联基因8(T-cell death associated gene 8,TDAG8)、G蛋白偶联受体4(G protein-coupled receptor 4,GPR4)及诱导细胞停滞于G2/M期的G蛋白偶联受体G2A(from G2 accumulation)4种受体是最新发现的一类质子感知受体.除了质子,体内又有它们各自特定的脂质分子配体活化这些受体来调节细胞机能.该类受体广泛分布于人的各种正常组织和肿瘤组织细胞中,在肿瘤的发生与转移、细胞骨架重组等生理病理过程中发挥双重作用.正常表达时它们有一定的抑制肿瘤作用,但这些受体的异常表达或过表达使某些组织和细胞恶性转化,导致肿瘤的发生.本文综述了在肿瘤组织的酸性微环境中,细胞表达的质子(pH)感知受体对肿瘤发生与肿瘤转移的调节作用及其相关的信号通路.

Ovarian cancer G protein-coupled receptor 1（OGR1）,G protein-coupled receptor 4（GPR4）,T-cell death associated gene 8（TDAG8）,and G2A（from G2 accumulation）are newly discovered proton sensing receptors which belong to the OGR1 subfamily.These receptors are activated by protons as well as some specific lipid ligands regulating normal cellular functions.They are widely expressed in both normal and tumor cells in human body,and may have dual function in a variety of physiological and pathological states including tumorigenesis,tumor metastasis,and rearrangement of cytoskeleton.Unusual or over expression of these receptors causes vicious transformation of some tissues or cells into tumor,although their normal expression inhibits tumorigenesis to some extent.In this article,we reviewed the regulatory role of these proton-sensing receptors on tumorigenesis and tumor metastasis,focusing on its function in tumor acidic microenvironment.The mechanism of its associated signaling pathway is also discussed.